U.S. patent application number 10/401469 was filed with the patent office on 2004-12-16 for reinforced implantable medical devices.
Invention is credited to Contiliano, Joseph H., Li, Yufu, Li, Zhigang, Roller, Mark B., Vyakarnam, Murty N., Yuan, Jenny J..
Application Number | 20040254639 10/401469 |
Document ID | / |
Family ID | 32825018 |
Filed Date | 2004-12-16 |
United States Patent
Application |
20040254639 |
Kind Code |
A1 |
Li, Zhigang ; et
al. |
December 16, 2004 |
Reinforced implantable medical devices
Abstract
The present invention is directed to reinforced, biocompatible,
biodegradable compositions suitable for use in implantable medical
devices and medical devices made at least in part from such
compositions, where the compositions include a biocompatible,
biodegradable polymer; a biocompatible, biodegradable wax; and
greater than about 30 weight percent of an inorganic filler
material.
Inventors: |
Li, Zhigang; (Hillsborough,
NJ) ; Roller, Mark B.; (North Brunswick, NJ) ;
Vyakarnam, Murty N.; (Edgewater, NJ) ; Yuan, Jenny
J.; (Neshanic Station, NJ) ; Contiliano, Joseph
H.; (Stewartsville, NJ) ; Li, Yufu;
(Bridgewater, NJ) |
Correspondence
Address: |
PHILIP S. JOHNSON
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
32825018 |
Appl. No.: |
10/401469 |
Filed: |
March 28, 2003 |
Current U.S.
Class: |
623/1.49 |
Current CPC
Class: |
A61L 31/125 20130101;
Y10S 525/937 20130101; A61L 31/127 20130101; A61L 31/148
20130101 |
Class at
Publication: |
623/001.49 |
International
Class: |
A61F 002/06 |
Claims
We claim:
1. A biocompatible, biodegradable composition suitable for use in
implantable medical devices, comprising: a biocompatible,
biodegradable polymer, a biocompatible, biodegradable wax; and
greater than about 30 weight percent of an inorganic filler
material.
2. The composition of claim 1 wherein the biodegradable polymer is
selected from the group consisting of aliphatic polyesters,
poly(amino acids), copoly(ether-esters), polyalkylenes oxalates,
polyamides, poly(ethylene glycol), poly(iminocarbonates),
polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters
containing amine groups, poly(anhydrides), polyphosphazenes,
biopolymers and copolymers thereof.
3. The composition of claim 2 wherein the aliphatic polyester is
selected from the group consisting of homopolymers and copolymers
of lactide, glycolide, epsilon-caprolactone, para-dioxanone,
trimethylene carbonate, alkyl derivatives of trimethylene carbonate
and monoglyceride polyesters.
4. The composition of claim 3 wherein the aliphatic polyester
comprises a copolymer of from about 80 to 99 mole percent lactide
and glycolide.
5. The composition of claim 4 wherein the aliphatic polyester has
an inherent viscosity of greater than about 2.0 g/dl as measured in
chloroform at 25.degree. C.
6. The composition of claim 1 wherein the biodegradable wax is
selected from the group consisting of aliphatic polyesters,
poly(amino acids), copoly(ether-esters), polyalkylenes oxalates,
polyamides, poly(ethylene glycol), poly(iminocarbonates),
polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters
containing amine groups, poly(anhydrides), polyphosphazenes,
biopolymers and copolymers thereof.
7. The composition of claim 6 wherein the aliphatic polyester wax
is selected from the group consisting of homopolymers and
copolymers of lactide, glycolide, epsilon-caprolactone,
para-dioxanone, trimethylene carbonate, alkyl derivatives of
trimethylene carbonate and monoglyceride polyesters.
8. The composition of claim 7 wherein the aliphatic polyester wax
comprises a copolymer of from about 90 to about 10 mole percent
epsilon-caprolactone and glycolic acid.
9. The composition of claim 8 wherein the wax has an inherent
viscosity of less than about 0.7 g/dl as measured in chloroform at
25.degree. C.
10. The composition of claim 1 wherein the inorganic filler
material is selected from the group consisting of mono-, di-, tri-,
.alpha.-tri-, .beta.-tri-, and tetra-calcium phosphate,
hydroxyapatite, fluoroapatites, calcium sulfates, calcium
fluorides, calcium oxides, calcium carbonates, magnesium calcium
phosphates and bio-glasses.
11. The composition of claim 10 wherein the inorganic filler
material comprises P-tricalcium phosphate.
12. A biodegradable implantable medical device, comprising a
biocompatible, biodegradable composition, the composition
comprising: a biocompatible, biodegradable polymer, a
biocompatible, biodegradable wax; and greater than about 30 weight
percent of an inorganic filler material.
13. The medical device of claim 12 wherein the biodegradable
polymer is selected from the group consisting of aliphatic
polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes
oxalates, polyamides, poly(ethylene glycol), poly(iminocarbonates),
polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters
containing amine groups, poly(anhydrides), polyphosphazenes,
biopolymers and copolymers thereof.
14. The medical device of claim 13 wherein the aliphatic polyester
is selected from the group consisting of homopolymers and
copolymers of lactide, glycolide, epsilon-caprolactone,
para-dioxanone, trimethylene carbonate, alkyl derivatives of
trimethylene carbonate and monoglyceride polyesters.
15. The medical device of claim 14 wherein the aliphatic polyester
comprises a copolymer of from about 80 to 99 mole percent lactide
and glycolide.
16. The medical device of claim 15 wherein the aliphatic polyester
has an inherent viscosity of greater than about 2.0 g/dl as
measured in chloroform at 25.degree. C.
17. The medical device of claim 12 wherein the biodegradable wax is
selected from the group consisting of aliphatic polyesters,
poly(amino acids), copoly(ether-esters), polyalkylenes oxalates,
polyamides, poly(ethylene glycol), poly(iminocarbonates),
polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters
containing amine groups, poly(anhydrides), polyphosphazenes,
biopolymers and copolymers thereof.
18. The medical device of claim 17 wherein the aliphatic polyester
wax is selected from the group consisting of homopolymers and
copolymers of lactide, glycolide, epsilon-caprolactone,
para-dioxanone, trimethylene carbonate, alkyl derivatives of
trimethylene carbonate and monoglyceride polyesters.
19. The medical device of claim 7 wherein the aliphatic polyester
wax comprises a copolymer of from about 90 to about 10 mole percent
epsilon-caprolactone and glycolic acid.
20. The medical device of claim 19 wherein the wax has an inherent
viscosity of less than about 0.7 g/dl as measured in chloroform at
25.degree. C.
21. The medical device of claim 12 wherein the inorganic filler
material is selected from the group consisting of mono-, di-, tri-,
.alpha.-tri-, .beta.-tri-, and tetra-calcium phosphate,
hydroxyapatite, fluoroapatites, calcium sulfates, calcium
fluorides, calcium oxides, calcium carbonates, magnesium calcium
phosphates and bio-glasses.
22. The medical device of claim 21 wherein the inorganic filler
material comprises .beta.-tricalcium phosphate.
23. The medical device of claim 12 selected from the group
consisting of reinforcing rods, plates, cages, screws, pins,
anchors, expanding sleeves and expanding collars.
24. The medical device of claim 23 wherein the anchor comprises a
radially-expandable sheath and a sheath-expanding element.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to reinforced, biocompatible,
biodegradable materials suitable for use in the fabrication of
implantable medical devices (IMDs) and biodegradable implantable
medical devices fabricated at least in part from such
materials.
BACKGROUND OF THE INVENTION
[0002] Implantable medical devices (IMDs) have been widely used for
more than 40 years in various surgical applications. For example,
in fracture fixation operations, IMDs are used to address bone
fractures by attaching a reinforcing rod or a plate or a cage to a
fractured bone so that the broken ends may be stabilized to promote
fusion and consequent healing. In sport medicine area, IMDs are
used to repair and augment soft tissues, such as anterior cruciate
ligament (ACL) replacement. IMDs such as screws are used to affix
autografts, allografts, xenografts, or bone fragments to bone
structure of a patient. In the case of ACL procedure, the torn ACL
is replaced by inserting an IMD in the form of interference screw
into a bone tunnel to secure one end of a replacement graft in
place.
[0003] Metal implants have often been used because of their high
stiffness and strength. However, several issues still remain. Metal
implants, being much stiffer than bone, become the primary
load-bearing member thereby protecting the bone from stress, which
results in undesirable stress shielding. It is often necessary to
perform a second surgical procedure to remove metal implants after
the bone tissues have healed.
[0004] The use of biodegradable materials, materials that degrade
in the body and then are either absorbed into or excreted from the
body, has the potential to eliminate the necessity of a second
operation and help alleviate the negative effects of stress
shielding. Biodegradable polymeric materials have been used as IMDs
in the form of pins, rods, anchors, screws, staples, and fasteners
for a variety of medical applications. However, relatively low
stiffness and strength of biodegradable devices compared with
metallic implants has limited their use to low-load bearing
applications or non-load bearing applications.
[0005] Inorganic fillers have been used as reinforcement to enhance
the mechanical properties of biodegradable polymeric materials.
Homopolymers and copolymers of L-lactic, DL-lactic and glycolic
acids reinforced with tricalcium phosphate ranging from 0 to 40
percent by weight were studied. Typically, composites of this
nature exhibit increased stiffness, but are characteristically
brittle.
[0006] In U.S. Pat. No. 6,165,486 (to Marra, et al.),
hydroxyapatite (HA) granules were incorporated into the blends of
poly(caprolactone) and poly(D,L-lactic-co-glycolic) acid for
replacing, augmenting or serving as a substitute for hard tissue
such as bone. Marra teaches that HA in the range of about 0 to 25
weight percent can be incorporated into the composition. Marra also
states, "If the tissue being replaced, augmented, or substituted or
the device being formed does not benefit from incorporation of a
mineralized component, it is advisable to substantially omit
hydroxyapatite from the blend. This is because incorporation of
hydroxyapatite results in a more "brittle" device. Minimal or no
hydroxyapatite is desirable where a brittle characteristic renders
the device or article less useful e.g., sutures, anchors, fixation
systems such as sutures, suture anchors, staples, surgical tacks,
clips, plates and screws. It is also advisable to avoid large
concentrations (i.e., above 10% by weight) of hydroxyapatite soft
tissue applications such as tissue used to substitute or augment
breast tissue."
[0007] Due to the inherent brittleness and lower strength of these
materials, ceramic filler-reinforced biodegradable polymers have
often been used in non- or low-load bearing applications such as
bone filler or cement.
[0008] In another aspect of medical procedures, the movement of a
surface of an implantable device with respect to tissue is
important in reducing damage to both the material of the surface
and to the tissue. Damage to tissue as a result of this tissue-drag
friction causes inflammation and pain to the patient and leads to a
longer recovery time. High friction between the surface material
and blood may result in clotting and subsequent occlusion of a
blood vessel. Friction may also damage the material, thus rendering
it ineffective or shortening its useful life.
[0009] In summary, the inherent brittleness and high stiffness of
biodegradable composite systems know to date have limited their
usefulness for applications in certain IMDs. In addition, there is
a need for methods of reducing device drag in biodegradable
composite IMDs while maintaining the degradable nature of the
devices.
SUMMARY OF THE INVENTION
[0010] The present invention is directed to reinforced,
biocompatible, biodegradable compositions suitable for use in
implantable medical devices and medical devices made at least in
part from such compositions, where the compositions comprise a
biocompatible, biodegradable polymer; a biocompatible,
biodegradable wax; and greater than about 30 weight percent of an
inorganic filler material. Devices according to the present
invention containing relatively high levels of filler material when
compared to conventional devices and possess properties such as
good elongation to failure, i.e. they are flexible and are
non-brittle, and high lubricity.
BRIEF DESCRIPTION OF THE FIGURES
[0011] FIG. 1 is a stress-strain curve of the tensile tests of four
different materials.
[0012] FIG. 2 is medical device of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0013] This present invention relates to biocompatible,
biodegradable polymeric composite compositions possessing improved
elongation to failure and lower surface friction. In addition to a
biocompatible, biodegradable polymer suitable for use in medical
devices, the compositions comprise a polymeric wax component and
greater than about 30 percent by weight of an inorganic filler
material used for the purpose of providing reinforcement properties
to the materials when utilized in the fabrication of medical
devices. The invention also relates to implantable medical devices
that are fabricated at least in part from such composition and
which possess properties such as good elongation to failure, i.e.
they flexible and are non-brittle, and high lubricity.
[0014] Implantable medical devices where compositions of the
present invention may be useful include, but are not limited to,
absorbable maxillofacial bone fixation plates, absorbable bone
screws or other fastening devices, absorbable surgical clips and
staples, absorbable devices with living hinges, and absorbable bone
fixation rods and screws. Potential also exists in applications
where two articulating surfaces come together and need a certain
lubricity, such as rivet/pin constructs and expanding sleeve or
collar devices.
[0015] In order to possess bulk properties suitable for processing
into medical devices, the composite materials preferably comprise a
continuous, biodegradable polymer phase, with the inorganic filler
and biodegradable wax components being dispersed substantially
homogenously there through. The individual components may be
blended together such that the filler and wax are homogeneously
dispersed through the polymer phase. Such blends then may be
further processed by standard methods of compounding, for example
extrusion or batch compounding, following by chopping of the
compounded material to form pellets and the like of the homogenous
blend. The pellets then may be used to prepare medical devices
according to the invention, for example by extrusion or compression
molding. Alternately, the individual components may be added
directly to a compounding and molding apparatus, for example an
extruder having the proper mixing screw configuration so as to
homogenously blend the components in the extrusion barrel, with the
extruder being fitted with the appropriate die to form medical
devices according to the invention. Once having the benefit of this
disclosure, one skilled in the art would be able to select the
proper parameters and specific apparatus required for the
particular blend of components and medical device being
fabricated.
[0016] The continuous polymer phase comprises a high molecular
weight, biocompatible, biodegradable polymer. High molecular weight
polymers, are defined herein, comprise polymers with an inherent
viscosity (IV) of greater than about 2.0 dl/g when measured in
chloroform at 25.degree. C. By biodegradable, it is meant that the
polymer may be degraded or otherwise broken down in the body such
that the components of the degraded polymer may be absorbed by or
otherwise passed from the body.
[0017] Examples of suitable biocompatible, biodegradable polymers
that could be used according to the present invention include,
without limitation, polymers selected from the group consisting of
aliphatic polyesters, poly(amino acids), copoly(ether-esters),
polyalkylenes oxalates, polyamides, poly(ethylene glycol),
poly(iminocarbonates), polyorthoesters, polyoxaesters,
polyamidoesters, polyoxaesters containing amine groups,
poly(anhydrides), polyphosphazenes, biopolymers, and copolymers and
blends thereof.
[0018] Aliphatic polyesters useful according to the present
invention include, but are not limited to, homopolymers and
copolymers of lactide (which includes lactic acid, D-,L- and meso
lactide), glycolide (including glycolic acid),
epsilon-caprolactone, para-dioxanone (1,4-dioxan-2-one),
trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of
trimethylene carbonate, monoglyceride polyesters, and polymer
blends thereof.
[0019] Preferred polymers utilized in the invention comprise
homopolymers of lactide (PLA) and homopolymers of glycolide (PGA).
More preferred are copolymers of PLA and PGA (PLGA), such
copolymers comprising from about 80 to about 95 mole percent
PLA.
[0020] The wax component of the present invention is a low
molecular weight biocompatible, biodegradable polymer with a low
coefficient of friction. Low molecular weight polymers are defined
herein comprise polymers with an Inherent Viscosity (IV) of less
than about 0.7 dl/g when measured in chloroform at 25.degree. C.
Preferably, the IV is between about 0.3 and 0.5 dl/g when measured
in chloroform at 25.degree. C. For the purposes of this invention,
a wax is defined as a polymer that is a solid at room temperature,
has a relatively low melting point, e.g. preferably below
100.degree. C., that is slippery and plastic when, and fluid when
melted.
[0021] Examples of suitable biocompatible, biodegradable waxes that
could be used include, without limitation low molecular weight
polymers selected from the group consisting of aliphatic
polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes
oxalates, polyamides, poly(ethylene glycol), poly(iminocarbonates),
polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters
containing amine groups, poly(anhydrides), polyphosphazenes,
biopolymers, and copolymers and blends thereof.
[0022] Aliphatic polyesters which can be made into a wax, as
defined herein, include, but are not limited to, homopolymers and
copolymers of lactide (including lactic acid, D-,L- and meso
lactide), glycolide (including glycolic acid),
.epsilon.-caprolactone, para-dioxanone (1,4-dioxan-2-one),
trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of
trimethylene carbonate, monoglyceride polyesters, and blends
thereof.
[0023] For example, monoglyceride polyester (MGPE) materials
suitable for this invention include biocompatible, biodegradable
aliphatic polyester waxes made by the polycondensation of
monoalkanoyl glycerides and common dicarboxylic acids These MGPEs
have an aliphatic polyester backbone with pendant fatty acid ester
groups and exhibit relatively low melting points
(T.sub.m<100.degree. C). Preferred waxes preferably have a
melting point of below about 80.degree. C., more preferably about
45.degree. C. to 60.degree. C.
[0024] Among the preferred wax materials are copolymers of lactide
(PLA) and glycolide (PGA) (PLGA); epsilon-caprolactone (PCL) and
lactide (PCLA); and epsilon-caprolactone and para-dioxanone (PDO)
(PCDO). A preferred wax material is a copolymer of 95 mole percent
PCL and about 5 mole percent PDO (95/5 PCDO).
[0025] The most preferred wax material comprises a copolymer of
epsilon-caprolactone and glycolide. This family of polymers is more
fully disclosed in U.S. Pat. No. 4,994,074, issued Feb. 19, 1991,
assigned to Ethicon Inc., which is hereby incorporated herein by
reference as if set forth in its entirely.
[0026] Most preferred are copolymers comprising about 90 mole
percent epsilon-caprolactone (PCL) and 10 mole percent glycolide
(PGA) (90/10 PCGA).
[0027] The biocompatible, biodegradable inorganic fillers of the
current 20 invention can be fine powders of ceramics comprising
mono-, di-, tri-, .alpha.-tri-, .beta.-tri-, and tetra-calcium
phosphate, hydroxyapatite, fluoroapatites, calcium sulfates,
calcium fluorides, calcium oxides, calcium carbonates, magnesium
calcium phosphates, bioglasses, or mixtures thereof.
[0028] As noted above, composite materials of this invention can be
melt processed by numerous methods to prepare a vast array of
useful devices. The compositions may be injection or compression
molded to make implantable medical devices for various surgical
applications. Examples of such devices include reinforcing rods,
plates, or cages used to aid in the stabilization of fractured
bone. Devices also include fixation devices, e.g. screws, pins, and
anchors, and expanding sleeve or collar devices, all used to repair
and/or augment soft tissues or to affix autografts, allografts,
xenografts, or bone fragments to the bone structure of a
patient.
[0029] FIG. 2 is an exemplary medical device formed using the
composition of the present invention. The device is a graft
ligament anchor. The design of the anchor components are disclosed
in U.S. patent application Ser. No. 09/966766, entitled "Graft
Ligament Anchor and Method for Attaching a Graft Ligament to a
Bone", filed Sep. 28, 2001, the disclosure of which is incorporated
by reference as if set forth in its entirety. The anchor comprises
radially-expandable sheath 400 and sheath-expanding element 700.
Other devices where compositions of the present invention may be
used will be readily apparent to those skilled in the art once
having the benefit of this disclosure.
[0030] Various bioactive agents such as proteins (including short
chain peptides), growth agents, chemotatic agents and therapeutic
agents can be added to the polymer or wax prior or during the time
of blending to make the implantable medical devices of the present
invention. In general, bioactive agents which may be administered
via pharmaceutical compositions of the invention include, without
limitation, antiinfectives, such as antibiotics and antiviral
agents; analgesics and analgesic combinations; anorexics;
antihelmintics; antiarthritics; antiasthmatic agents;
anticonvulsants; antidepressants; antidiuretic agents;
antidiarrheals; antihistamines; antiinflammatory agents;
antimigraine preparations; antinauseants; antineoplastics;
antiparkinsonism drugs; antipruritics; antipsychotics;
antipyretics; antispasmodics; anticholinergics; sympathomimetics;
xanthine derivatives; cardiovascular preparations including calcium
channel blockers and beta-blockers such as pindolol and
antiarrhythmics; antihypertensives; diuretics; vasodilators,
including general coronary, peripheral and cerebral; central
nervous system stimulants; cough and cold preparations, including
decongestants; hormones, such as estradiol and other steroids,
including corticosteroids; hypnotics; immunosuppressives such as
rapamycin; muscle relaxants; parasympatholytics; psychostimulants;
sedatives; tranquilizers;
[0031] naturally derived or genetically engineered proteins, growth
factors, polysaccharides, glycoproteins or lipoproteins;
oligonucleotides; antibodies; antigens; cholinergics;
chemotherapeutics; hemostatics; clot dissolving agents;
[0032] radioactive agents; and cystostatics.
[0033] Growth factors include bone morphogenic proteins (i.e. BMPs
1-7), bone morphogenic-like proteins (i.e. GFD-5, GFD-7 and GFD-8),
epidermal growth factor (EGF), fibroblast growth factor (i.e. FGF
1-9), platelet derived growth factor (PDGF), insulin like growth
factor (IGF-I and IGF-II), transforming growth factors (i.e.
TGF-.beta.I-III), and vascular endothelial growth factor
(VEGF).
[0034] The following examples are illustrative of the principles
and practice of this invention, although not limited thereto.
Numerous additional embodiments within the scope and spirit of the
invention will become apparent to those skilled in the art once
having the benefit of this disclosure. Unless stated otherwise, the
Inherent Viscosity (IV) of the polymers and waxes disclosed herein
were measured in chloroform at 25.degree. C.
EXAMPLE 1
[0035] Compounding a composite blend of hydroxyapatide (HA),
poly(epsilon-caprolactone) (PCL), and a 65/35 copolymer of lactide
(PLA) and glycolide (PGA), or 65/35 poly(DL-lactide-co-glycolide)
(65/35 PLGA).
[0036] 91.5 grams of HA (Aldrich, Milwaukee, Wis.), 36.6 grams of
65/35 PLGA (BPI, Birmingham Polymers Inc., Birmingham, Ala.,
IV=0.66 dl/g) and 238.0 grams of PCL (Aldrich, Milwaukee, Wis.,
Molecular weight 42,500-65,000) were weighted out separately. The
resultant weight ratio of the three components was 25/10/65. A
model REE6 Prep-Mixer (Brabender, South Hakensack, NJ) with cam
blades was chosen to compound the blend. The PLGA, PCL and HA were
fed into the mixing bowl sequentially.
[0037] The compounding process conditions were as follows: 1) mixer
was preheated to 180.degree. C., 2) blade speed set to 50 rpm, and
3) mixing time was 15 minutes after all the materials were fed.
After compounding, the mixture was cooled, ground using a Wiley
grinder, The ground material then was dried in a vacuum oven at
55.degree. C. for 48 hours under a vacuum of 1 Torr and then stored
at room temperature under vacuum for future processing.
EXAMPLE 2
[0038] Injection-Molding of tensile testing coupons using the
material compounded in Example 1.
[0039] Tensile testing coupons (ASTM type V) of the material made
in Example 1 were formed by injection molded using a 35-ton
injection-molding machine (model NN35M14, Niigata LTD, Niigata,
Japan). The processing conditions were as follows: 1) temperature
profile 200, 230, 230, 220.degree. C. from rear to nozzle, 2)
injection pressure 26,640 psi, 3) holding pressure 20,980 psi, 4)
injection speed set to 200 mm/second, 5) total time of injection
and holding segments 2.5 seconds, and 6) cooling time 25
seconds.
Example 3
[0040] Compounding a composite blend of tricalcium phosphate (TCP),
poly(lactide) poymer (PLA), and a 90/10 wax of epsilon-caprolactone
(PCL) and glycolide (PGA), or 90/10 poly(caprolactone-co-glycolide)
(90/10 PCGA).
[0041] PLA polymer (Purac, Gorinchem, The Netherlands, IV=2.37
g/dl) and 90/10 PCGA wax (Ethicon, Incorporated, Somerville, N.J.,
IV=0.3.about.0.5 g/dl) were dry premixed in the weight ratio of
61/9. An 18-mm co-rotation twin-screw extruder (Model micro 18
GL/35, Leistritz, Somerville, NJ) was used in the compounding
process. The PLA/PCGA premix was fed using a gravimetlic feeder at
a feed rate of 3.47 lbs/hr. The TCP powder (CAM Implants, Leiden,
The Netherlands) was fed using a second gravimetric feeder at a
feed rate of 1.53 lbs/hr. The resulting blend was 30 weight percent
TCP, 6.3 weight percent PCGA, and 63.7 weight percent PLA (or 30/70
TCP/(9/91 (PCGA)/PLA).
[0042] The compounding process conditions, using a low to medium
shear screw design, were as follows: 1) temperature profile from
hopper to die was 100, 195, 195, 195, 190, 190, 190.degree. C., 2)
screw speed 150 rpm, 3) total feed rate 5 lbs/hr, 4) melt pressure
about 630 psi, and 5) torque about 38 percent. The extrudate was
cooled using an air cooling conveyer, pelletized and stored at room
temperature under vacuum for future processing.
EXAMPLE 4
[0043] Compounding a blend of poly(lactide) (PLA), and a 90/10 wax
of epsilon-caprolactone (PCL) and glycolide (PGA), or 90/10
poly(caprolactone-co-glycolide) (90/10 PCGA).
[0044] PLA polymer and 90/10 PCGA wax as described in Example 3
were dry premixed in the weight ratio of 91/9. The 18-mm
co-rotation twin-screw extruder from Example 3 was used in the
compounding process. The PLA/PCGA premix was fed using a
gravimetric feeder at a feed rate of 5.0 lbs/hr.
[0045] The compounding process conditions, using a low to medium
shear screw design, were the same as Example 3, except melt
pressure was about 650 psi, and torque was about 32 percent. The
extrudate was cooled using an air cooling conveyer, pelletized and
stored at room temperature under vacuum for future processing. The
resulting blend was 91/9 PLA/(90/10 PCGA).
EXAMPLE 5
[0046] Compounding a composite blend of tricalcium phosphate (TCP)
and poly(lactide) polymer (PLA).
[0047] PLA polymer and TCP as described in Example 3 were used, as
was the 18-mm co-rotation twin-screw extruder. The PLA was fed
using a gravimetric feeder at a feed rate of 2.091 lbs/hr. The TCP
powder was fed using a second gravimetric feeder at a feed rate of
0.909 lbs/hr. The resulting blend was 30 weight percent TCP, and 70
weight percent PLA (or 30/70 TCP/PLA).
[0048] The compounding process conditions, using a low to medium
shear screw design, were as follows: 1) temperature profile from
hopper to die was 190, 200, 190, 190, 190, 200, 200.degree. C., 2)
screw speed 250 rpm, 3) total feed rate 3 lbs/hr, 4) melt pressure
about 1,700 psi, and 5) torque about 85 percent. The extrudate was
cooled using an air cooling conveyer, pelletized and stored at room
temperature under vacuum for future processing.
EXAMPLE 6
[0049] Injection-Molding of tensile testing coupons using the
material compounded in Examples 3, 4, and 5.
[0050] Tensile testing coupons (ASTM type V) of the materials made
in Examples 3, 4, and 5 were injection molded using the 35-ton
injection molding machine described in Example 2. Neat PLA, as
described in Example 3 also was injection molded.
[0051] The processing conditions were as follows: 1) temperature
profile 350, 390, 400, 400.degree. F. from rear to nozzle, 2)
injection pressure 26,640 psi, 3) holding pressure 20,970 psi, 4)
injection speed set to 200 mm/second, 5) total time of injection
and holding segments 5 seconds, and 6) cooling time 25 seconds.
EXAMPLE 7
[0052] Tensile properties of the materials injection molded in
Examples 2 and 6.
[0053] The ASTM tensile type V tensile coupons injection molded in
Examples 2 and 6 were tested in tension using an Instron 4201
tested with Instron series IX data analysis software. A
video-extensometer was used for elongation measurement.
[0054] Tensile stress-strain curves for all or the materials are
shown on FIG. 1. The figure shows the neat PLA had a yield point
and a strain to failure of about 150 percent.
[0055] The addition of 30 weight percent TCP to PLA, or 30/70
TCP/PLA, significantly reduced the failure strain to about 3
percent, and the composite broke with no yielding behavior. So, the
addition of TCP to PLA made the PLA more brittle.
[0056] The addition of 9 weight percent 90/10 PCGA wax to the PLA
polymer, or 91/9 PLA/(90/10 PCGA), also showed a reduced strain to
failure. This material had a yield point, and the strain to failure
was about 50 percent. It is apparent that the addition of wax into
PLA made the PLA more brittle.
[0057] In the fourth material system, in which 30 weight percent
TCP and 9 weight percent PCGA wax were added to PLA polymer, the
stress-strain curve showed a yield point and a strain to failure of
20 percent. This result was a surprise as the 30/70 TCP/(9/91
(PCGA)/PLA) composite had much higher value of strain to failure
compared to 30/70 TCP/PLA. It is apparent that instead of
increasing the brittleness of the 30/70 TCP/PLA material, the
addition of wax toughened the composite.
EXAMPLE 8
[0058] Process for forming exemplary medical device using the
material of the present invention.
[0059] Bioabsorbable graft ligament anchor components as shown in
FIG. 2 were manufactured using an injection molding process.
[0060] The polymer used to make the radially-expandable sheath
elements 400 was PLA, (Purac, Gorinchem, The Netherlands, IV of
1.87 dL/g as measured in chloroform). Sheath-expanding elements 700
were formed using the PLA described in this example, and 30/70
TCP/(9/91(PCGA)/PLA), 91/9 PLA/(90/10 PCGA), and 30/70 TCP/PLA
described in Examples 3, 4, and 5, respectively.
[0061] All parts were injection molded using the 35-ton
injection-molding machine described in Example 2. The processing
conditions for the expandable sheath elements were as follows: 1)
temperature profile 300, 400, 410, 420.degree. F. from rear to
nozzle, 2) injection pressure 15000 psi, 3) holding pressure 13700
psi, 4) injection speed set to 200 mm/second, 5) total time of
injection and holding segments 2 seconds.
EXAMPLE 9
[0062] Torque forces required to engage the graft ligament anchor
device of Example 8.
[0063] The torque forces required to insert the sheath-expanding
elements into the radially-expandable sheaths described in Example
8 were measured. The method was as follows: Pilot holes, 11.5 mm in
diameter, were drilled in a model bone material (#25 Sawbone,
Pacific Research, Vashon, Wash.). Four GORE-TEX Joint Sealants
(1/4-inch diameter), sold by W. L. Gore & Associates, Inc.,
Elkton, Md., were placed in each quadrant of the pilot hole to
simulate hamstring tendons. A radially-expandable sheath was
inserted inside the pilot hole so that the joint sealants were
between the sheath and the walls of the pilot hole. The distal end
of a sheath-expanding element was inserted into the central lumen
of the expandable sheath. A digital torque gauge (Digital Torque
Gauge Model TMG, IMADA Incorporated, Northbrook, IL) was used to
measure the insertion torque. The digital torque gauge was a driver
connected to a torque meter so that the torque was measured while
driving the sheath-expanding element into the expandable
sheath.
[0064] The driver was disposed into the central cannulation of the
sheath-expanding element.
[0065] The peak insertion torque values required to drive the
expanding element into the sheath central lumen for PLA, 30/70
TCP/(9/91(PCGA)/PLA), and 91/9 PLA/(90/10 PCGA) expanding elements
were 30+, 15, and 12 in-lb, respectively. The 30/70 TCP/PLA
expanding sheath was brittle and broke during the insertion, so no
peak torque was determined for this material.
* * * * *